Вид документа : Статья из журнала
Шифр издания : 54/S 45
Автор(ы) : Rozov F.N., Grinenko T.S., Levit G. L., Krasnov V. P., Belyavskii A.V.
Заглавие : Selection of genetically modified hematopoietic cells in vitro and in vivo using alkylating agent lysomustine
Место публикации : Analytical Biochemistry . - 2010. - Vol. 404, № 2. - С. 149-154
ББК : 54
Предметные рубрики: ХИМИЧЕСКИЕ НАУКИ
Аннотация: Efficient gene transfer into hematopoietic stem cells is vital for the success of gene therapy of hematopoietic and immune system disorders. An in vivo selection system based on a mutant form of the O6-methylguanine-DNA-methyltransferase gene (MGMTm) is considered one of the more promising strategies for expansion of hematopoietic cells transduced with viral vectors. Here we demonstrate that MGMTm-expressing cells can be efficiently selected using lysomustine, a nitrosourea derivative of lysine. K562 and murine bone marrow cells expressing MGMTm are protected from the cytotoxic action of lysomustine in vitro. We also show in a murine model that MGMTm-transduced hematopoietic cells can be expanded in vivo on transplantation into sublethally irradiated recipients followed by lysomustine treatment. These results indicate that lysomustine can be used as a potent novel chemoselection drug applicable for gene therapy of hematopoietic and immune system disorders
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Доп.точки доступа:
Rozov, F.N.; Grinenko, T.S.; Levit, G. L.; Левит Галина Львовна; Krasnov, V. P.; Belyavskii, A.V.